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1.
Rinsho Ketsueki ; 65(3): 169-174, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38569861

RESUMO

A 44-year-old woman was diagnosed with acute myeloid leukemia (RUNX1::RUNX1T1 translocation) and received induction chemotherapy with idarubicin hydrochloride and cytosine arabinoside. The pneumonia that had been present since admission worsened, and a drug-induced skin rash appeared. On day 17, she presented with respiratory failure and shock, complicated by hemoconcentration and hypoalbuminemia. This was considered capillary leak syndrome due to pneumonia and drug allergy, so she was started on pulse steroid therapy and IVIG, and was intubated on the same day. On day 18, venovenous-extracorporeal membrane oxygenation (VV-ECMO) was started due to worsening blood gas parameters despite ventilatory management. Bronchoalveolar lavage fluid was serous, and both blood and sputum cultures yielded negative. The patient was weaned from VV-ECMO on day 26 as the pneumonia improved with recovery of hematopoiesis. She was disoriented, and a CT scan on day 28 revealed cerebral hemorrhage. Her strength recovered with rehabilitation. After induction chemotherapy, RUNX1::RUNX1T1 mRNA was not detected in bone marrow. The patient received consolidation chemotherapy, and has maintained complete remission. Severe respiratory failure during induction chemotherapy for acute leukemia can be fatal, but VV-ECMO may be lifesaving.


Assuntos
Síndrome de Vazamento Capilar , Oxigenação por Membrana Extracorpórea , Leucemia Mieloide Aguda , Pneumonia , Insuficiência Respiratória , Humanos , Feminino , Adulto , Subunidade alfa 2 de Fator de Ligação ao Core , Quimioterapia de Indução , Síndrome de Vazamento Capilar/complicações , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia
2.
Front Immunol ; 15: 1359113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38571944

RESUMO

Acute Myeloid Leukemia (AML) is the prototype of cancer genomics as it was the first published cancer genome. Large-scale next generation/massively parallel sequencing efforts have identified recurrent alterations that inform prognosis and have guided the development of targeted therapies. Despite changes in the frontline and relapsed standard of care stemming from the success of small molecules targeting FLT3, IDH1/2, and apoptotic pathways, allogeneic stem cell transplantation (alloHSCT) and the resulting graft-versus-leukemia (GVL) effect remains the only curative path for most patients. Advances in conditioning regimens, graft-vs-host disease prophylaxis, anti-infective agents, and supportive care have made this modality feasible, reducing transplant related mortality even among patients with advanced age or medical comorbidities. As such, relapse has emerged now as the most common cause of transplant failure. Relapse may occur after alloHSCT because residual disease clones persist after transplant, and develop immune escape from GVL, or such clones may proliferate rapidly early after alloHSCT, and outpace donor immune reconstitution, leading to relapse before any GVL effect could set in. To address this issue, genomically informed therapies are increasingly being incorporated into pre-transplant conditioning, or as post-transplant maintenance or pre-emptive therapy in the setting of mixed/falling donor chimerism or persistent detectable measurable residual disease (MRD). There is an urgent need to better understand how these emerging therapies modulate the two sides of the GVHD vs. GVL coin: 1) how molecularly or immunologically targeted therapies affect engraftment, GVHD potential, and function of the donor graft and 2) how these therapies affect the immunogenicity and sensitivity of leukemic clones to the GVL effect. By maximizing the synergistic action of molecularly targeted agents, immunomodulating agents, conventional chemotherapy, and the GVL effect, there is hope for improving outcomes for patients with this often-devastating disease.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Efeito Enxerto vs Leucemia , Recidiva
3.
BMJ Case Rep ; 17(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38565228

RESUMO

We present a rare case of myeloid sarcoma in the stomach of an elderly woman initially diagnosed with anaemia. Myeloid sarcoma, an unusual extramedullary manifestation of acute myeloid leukaemia (AML), primarily affects lymph nodes, bones, spine and skin, with gastrointestinal involvement being infrequent. Despite normal results from the initial endoscopy, a follow-up examination after 4 months revealed multiple submucosal gastric tumours. These developments coincided with worsening of anaemia and an increase in peripheral myeloblasts. Pathological evaluation and immunohistochemical staining confirmed gastric extramedullary infiltration associated with AML. This case highlights the importance of comprehensive diagnostic processes when suspecting leukaemic transformations, especially in myelodysplastic syndrome (MDS). Due to financial constraints, additional critical studies such as cytogenetics and next-generation sequencing were not performed. Nonetheless, this rare case demonstrates the visual observation of rapid progression from MDS to AML and concurrent early myeloid sarcoma development in an elderly patient.


Assuntos
Anemia , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Neoplasias de Tecido Conjuntivo , Sarcoma Mieloide , Neoplasias Gástricas , Feminino , Humanos , Idoso , Sarcoma Mieloide/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/complicações , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patologia , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/patologia , Neoplasias de Tecido Conjuntivo/complicações , Anemia/complicações
4.
Clin Lab ; 70(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38623673

RESUMO

BACKGROUND: Infection may lead to agranulocytosis due to bone marrow suppression. However, a rare case with infection presented with morphological features of acute myeloid leukemia (AML). METHODS: We report a case of extreme agranulocytosis due to severe infection mimicking acute myeloid leukemia. The case was definitively diagnosed by subsequent morphology, flow cytometry, and bone marrow biopsy, and subsequent successful anti-infective treatment confirmed the diagnosis. CONCLUSIONS: To date, no case of a patient diagnosed with severe infection mimicking AML has been reported. The case emphasizes the importance of an integrated diagnostic work-up, especially careful clinical observation and differential diagnosis.


Assuntos
Agranulocitose , Leucemia Mieloide Aguda , Humanos , Medula Óssea/patologia , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Diagnóstico Diferencial , Citometria de Fluxo , Agranulocitose/diagnóstico , Agranulocitose/patologia
5.
Clin Lab ; 70(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38623681

RESUMO

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. It is a rare and challenging clinical presentation. For decades, there has been no treatment course for managing BPDCN and its overall prognosis is poor. METHODS AND RESULTS: We report a 27-year-old man who was admitted to the hospital due to an orbital tumor as the first symptom. Progressive enlargement of the orbital tumor was accompanied by multiple purple circular nodules on the body trunk. Pathological confirmation of BPDCN after resection of the orbital mass. Bone marrow smear and flow cytometry on examination indicate AML-M5. Performance of chemotherapy and peripheral blood autologous stem cell transplantation. CONCLUSIONS: The clinical manifestations of blastic plasmacytoid dendritic cell neoplasms are diverse. The diagnosis of BPDCN can be difficult due to overlapping morphologic, immunophenotypic, and clinical features of other hematologic AML. Relapsed and refractory BPDCN remains an elusive therapeutic challenge. The future of new targeted therapeutic drugs is expected.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Neoplasias Orbitárias , Neoplasias Cutâneas , Masculino , Humanos , Adulto , Neoplasias Orbitárias/diagnóstico , Neoplasias Orbitárias/complicações , Neoplasias Orbitárias/patologia , Células Dendríticas , Transplante Autólogo , Neoplasias Cutâneas/patologia , Neoplasias Hematológicas/diagnóstico , Leucemia Mieloide Aguda/complicações
6.
Ann Hematol ; 103(5): 1775-1777, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38556531

RESUMO

Pure red cell aplasia (PRCA) is a rare bone marrow (BM) disorder characterized by ineffective erythropoiesis, reduced reticulocyte count, normocytic anemia, and the absence of erythroid precursors. Here, we present a rare instance of PRCA occurring after ABO-matched allo-HSCT in a refractory/relapsed acute myeloid leukemia (R/R AML) patient. In this case, the patient received a combination treatment of Gilteritinib, Venetoclax, and Azacitidine. Remarkably, this treatment not only reduced myeloblasts but also facilitated the restoration of erythroid hematopoiesis.


Assuntos
Compostos de Anilina , Doenças da Medula Óssea , Compostos Bicíclicos Heterocíclicos com Pontes , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Pirazinas , Aplasia Pura de Série Vermelha , Sulfonamidas , Humanos , Azacitidina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Aplasia Pura de Série Vermelha/etiologia , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/complicações , Doenças da Medula Óssea/complicações
8.
BMC Nephrol ; 25(1): 113, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519911

RESUMO

BACKGROUND: Women are counseled preconceptionally about the potential risks of rAML progression and chance of complications during and due to pregnancy. However, a systematic search investigating the evidence on which this advice is based does not exist. The aim of this systematic review is to determine the effect of pregnancy on renal angiomyolipoma (rAML) size and risk of haemorrhage in patients with tuberous sclerosis complex (TSC). METHODS: We searched PubMed, EMBASE, Medline and ClinicalTrials.gov using terms for "renal angiomyolipoma" and "pregnancy". English-language articles published between January 1st 2000, and December 31st 2020 of which full-text was available were included. The initial search resulted in 176 articles. After the screening process we included 45 case reports and 1 retrospective study. For the retrospective study we assessed the risk of bias using the Newcastle-Ottawa Scale. We included articles about renal AML and pregnancy with and without an established diagnosis of TSC. From these articles we recorded the rAML sizes and rAML complications. RESULTS: Seven case reports, from a total of 45 case reports, provided follow-up data on renal AML size (these were all cases of renal AML without a known diagnosis of TSC). Of these cases, renal AML size decreased in one patient, was stable in one patient, increased in three patients and fluctuated in two others. Renal AML size of women who suffered a haemorrhage were significantly larger (12.1 ± 4.6 cm) than rAMLs of women who did not suffer a haemorrhage (8.3 ± 3.2 cm). Data from the retrospective study showed no difference in renal complications between the women with and without a history of pregnancy. Haemorrhage occurred in 30% of the women with a history of pregnancy (n = 20) and in 11% in the patients without a history of pregnancy (n = 2), however this retrospective study had methodological limitations. CONCLUSION: The effect of pregnancy on renal AML size and complications in patients with TSC is unclear. More research is needed to determine the risk of pregnancy on TSC-associated kidney disease in TSC patient.


Assuntos
Angiomiolipoma , Neoplasias Renais , Leucemia Mieloide Aguda , Esclerose Tuberosa , Humanos , Feminino , Gravidez , Angiomiolipoma/complicações , Neoplasias Renais/complicações , Esclerose Tuberosa/complicações , Estudos Retrospectivos , Hemorragia/etiologia , Leucemia Mieloide Aguda/complicações
9.
Vestn Oftalmol ; 140(1): 72-78, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38450469

RESUMO

The article presents a clinical case of bilateral Terson syndrome caused by the manifestation of acute myeloid leukemia. A 32-year-old man complained of a sharp decrease in vision in both eyes. Spontaneous subarachnoid hemorrhage occurred secondary to acute myeloid leukemia. Uncorrected visual acuity (UCVA) amounted to OD=0.01, OS=0.005. The anterior segment was normal in both eyes, voluminous immobile white-gray mass measuring 7-9 DD that completely covered the macula (intense hyperechoic cell suspension with a volume of about 1/2 of the vitreous cavity, ultrasound B-scan) were visualized in the posterior pole of the vitreous body of both eyes under conditions of maximum drug-induced mydriasis. Diagnosis: vitreous hemorrhage due to subarachnoid hemorrhage in both eyes secondary to acute myeloid leukemia. Vitrectomy was performed in both eyes. UCVA increased to 0.05 in both eyes. Vitrectomy contributed to improvement of visual functions and patient quality of life.


Assuntos
Leucemia Mieloide Aguda , Hemorragia Vítrea , Masculino , Humanos , Adulto , Hemorragia Vítrea/diagnóstico , Hemorragia Vítrea/etiologia , Hemorragia Vítrea/cirurgia , Qualidade de Vida , Corpo Vítreo , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Vitrectomia
10.
Front Immunol ; 15: 1335341, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545096

RESUMO

Introduction: Unmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also induce severe Graft-versus-Host-Disease (GvHD). To improve the balance between GvL and GvHD, it is crucial to identify factors that influence the alloreactivity of DLI. Methods: We investigated the effects of the presence of patient-derived antigen-presenting cells at time of DLI as estimated by the bone marrow (BM) chimerism status, lymphopenia as measured by the absolute lymphocyte count (ALC) at time of DLI, and the presence of a viral infection (de novo or reactivation) close to DLI on the risk of GvHD after DLI. The cohort consisted of patients with acute leukemia or myelodysplastic syndrome who prophylactically or pre-emptively received DLI as standard care after alemtuzumab-based alloSCT. In patients at high risk for relapse, DLI was administered at 3 months after alloSCT (n=88) with a dose of 0.3x106 or 0.15x106 T cells/kg in case of a related or unrelated donor, respectively. All other patients (n=76) received 3x106 or 1.5x106 T cells/kg, respectively, at 6 months after alloSCT. Results: For both DLIs, patients with reduced-intensity conditioning and an unrelated donor had the highest risk of GvHD. For DLI given at three months, viral infection within 1 week before and 2 weeks after DLI was an additional significant risk factor (hazard ratio (HR) 3.66 compared to no viral infection) for GvHD. At six months after alloSCT, viral infections were rare and not associated with GvHD. In contrast, mixed BM chimerism (HR 3.63 for ≥5% mixed chimerism compared to full donor) was an important risk factor for GvHD after DLI given at six months after alloSCT. ALC of <1000x106/l showed a trend for association with GvHD after this DLI (HR 2.05 compared to ≥1000x106/l, 95% confidence interval 0.94-4.45). Furthermore, the data suggested that the presence of a viral infection close to the DLI at three months or ≥5% mixed chimerism at time of the DLI at six months correlated with the severity of GvHD, thereby increasing their negative impact on the current GvHD-relapse-free survival. Conclusion: These data demonstrate that the risk factors for GvHD after DLI depend on the setting of the DLI.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Viroses , Humanos , Linfócitos T , Transfusão de Linfócitos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/complicações , Doadores não Relacionados , Viroses/complicações
11.
J Mycol Med ; 34(1): 101461, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38310659

RESUMO

Antifungal prophylaxis with a mold-effective agent has led to a substantial decrease in invasive infections caused by Aspergillus spp. in the management of patients with acute myeloid leukemia undergoing induction chemotherapy. However, difficult-to-treat infections caused by other molds, such as Fusarium, Lomentospora, and Scedosporium species may still complicate the neutropenic period. Here, we present a case of a 23-year-old woman with acute myeloid leukemia who developed a breakthrough invasive fungal rhinosinusitis caused by Fusarium proliferatum/annulatum on posaconazole prophylaxis. The infection was diagnosed using clinical, microbiological, and radiological criteria and the isolate was identified using Matrix Assisted Lazer Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) and sequencing. We searched Pubmed with "Fusarium proliferatum", "Fusarium annulatum", "immunosuppression AND fusariosis", "rhinosinusitis AND Fusarium proliferatum" and summarized the English literature for similar rhinosinusitis cases infected with the same pathogen.


Assuntos
Fusariose , Fusarium , Leucemia Mieloide Aguda , 60523 , Feminino , Humanos , Adulto Jovem , Adulto , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Fusariose/diagnóstico , Fusariose/tratamento farmacológico , Fusariose/microbiologia , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico
12.
Cancer Med ; 13(3): e7003, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38400682

RESUMO

BACKGROUND: Acute myeloid leukemia (AML) with myelodysplasia-related characteristics is a heterogeneous subset of AML that has been challenged throughout the history of myeloid malignancies classifications, considered to have similar outcomes as intermediate- or adverse-risk AML depending on the subgroup. However, little is known about the fate of these patients in refractory or relapsed situation (R/R) after first line therapy. METHODS: A large series of R/R AML patients, recorded in the French DATAML registry, have received either intensive chemotherapy (ICT), azacitidine (AZA) as single agent, or best supportive care (BSC). A cohort of 183 patients (median age 63-year-old) with what was called at the time AML-MRC has been explored, and data are reported here. RESULTS: Patient status was refractory for 93, while 90 had relapsed. Respectively, 88, 34, and 61 were included in the three treatment arms. The median OS of the whole cohort was 4.2 months (95%CI: 3.1-5.6) with a mean 1-year overall survival of 24% ± 3.2%. There was no significant survival difference between refractory and relapsed patients. The BSC group had overall a significantly worse outcome (p = 0.0001), and this remained true in both refractory (p = 0.01) and relapsed (p = 0.002) patients. Similar survivals were observed in both groups comparing ICT and AZA. CONCLUSIONS: These data, reporting about an ill-explored population, indicate the poor prognosis of this condition where both ICT and AZA can be proposed. The latter, which was demonstrated here to be a feasible option, should be added to new targeted therapies.


Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/tratamento farmacológico , Recidiva
14.
PLoS One ; 19(2): e0297805, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38363781

RESUMO

BACKGROUND: Leukemia cutis (LC) is an extramedullary acute myeloid leukemia (AML) infiltrate. No previous study has described the clinical characteristics and outcomes of Thai patients diagnosed with AML with LC. MATERIALS AND METHODS: We conducted a 7-year retrospective case-control study on Thai AML patients at Siriraj Hospital from November 2013 to July 2020. Patients were divided into LC and non-LC groups. Initial clinical presentations and laboratory findings were examined to identify LC-associated factors. Overall survival (OS) and relapse-free survival (RFS) were assessed. Pathological tissues underwent re-evaluation to validate the LC diagnoses. RESULTS: The study included 159 patients in a 2:1 ratio (106 non-LC and 53 LC). The LC group had a mean ± SD age of 54.3 ± 15.5 years; females were predominant. Three-fifths of the LC patients had intermediate-risk cytogenetics; 20.4% had an adverse risk, and 10.2% had a favorable risk. Most were classified as AML-M4 and AML-M5. Leukemic nodules were the primary finding in 58.5% of the cases, mainly on the legs. In the multivariate analysis of predictive factors associated with LC, organomegalies, specifically hepatomegaly, and lymphadenopathy, remained significant factors associated with LC [OR 4.45 (95%CI 1.20, 16.50); p = 0.026 and OR 5.48 (95%CI 1.65, 18.20); p = 0.005], respectively. The LC group demonstrated a significantly reduced OS (log-rank test p = 0.002) (median OS of 8.6 months vs. 32.4 months). RFS was considerably lower in the LC group (log-rank test p = 0.001) (median duration of 10.3 months vs. 24.4 months in the non-LC). CONCLUSIONS: AML patients who developed LC tended to experience notably poorer prognoses. Therefore, it is imperative to consider aggressive treatment options for such individuals. The presence of organomegalies in AML patients serves as a strong predictor of the possible occurrence of LC when accompanied by skin lesions.


Assuntos
Leucemia Monocítica Aguda , Leucemia Mieloide Aguda , Neoplasias Cutâneas , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Estudos de Casos e Controles , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patologia , Neoplasias Cutâneas/complicações , Recidiva , Prognóstico
15.
JCO Glob Oncol ; 10: e2300313, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38301180

RESUMO

PURPOSE: This study aimed to identify the patient characteristics of children with febrile neutropenia, the associated bacterial organisms, and their sensitivity patterns. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted at the Moi Teaching and Referral Hospital (MTRH) pediatric oncology ward, from June 2021 to April 2022. A total of 110 children who developed fever and neutropenia during chemotherapy were enrolled. Blood samples for culture were collected aseptically. Patient characteristics were presented in frequency tables. Antimicrobial sensitivity patterns were plotted in tables against the bacterial isolates cultured. Chi-square/Fisher's exact test was used to determine any association between patient characteristics, bacterial growth, and antimicrobial sensitivity. RESULTS: The majority (n = 66; 60%) were males. The median age was 6.3 years (standard deviation, 3.7). The majority of patients 71 (64.5%) had hematologic malignancies, the most common being AML. There was a significant association between severity of neutropenia and hematologic malignancies (P = .028). In total, 31/110 (28.2%) blood cultures were positive for bacterial growth. Gram-positive bacteria were more frequent (n = 20; 58.1%). The most common organism was Escherichia coli (n = 6; 18.2%), followed by Staphylococcus aureus (n = 5; 15.2%). All the isolates were sensitive to linezolid and vancomycin and also showed good sensitivity toward meropenem (n = 10/11; 90.9%). High resistance to cephalosporins was noted with ceftriaxone (n = 5/6; 83.3%), cefepime (n = 4/7; 57.1%), and ceftazidime (n = 3/4; 75%). CONCLUSION: The most common malignancy associated with febrile neutropenia was AML. Gram-positive bacteria were the most common isolates. There was high resistance to cephalosporins.


Assuntos
Bacteriemia , Neutropenia Febril , Neoplasias Hematológicas , Leucemia Mieloide Aguda , Masculino , Criança , Humanos , Feminino , Antibacterianos/efeitos adversos , Centros de Atenção Terciária , Estudos Transversais , Quênia , Bacteriemia/complicações , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Cefalosporinas/efeitos adversos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/microbiologia , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/epidemiologia , Neutropenia Febril/complicações , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico
16.
Bone Marrow Transplant ; 59(4): 541-549, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38321271

RESUMO

This study aimed to address the prognostic impact of center experience based on the data of 7821 adults with acute myeloid leukemia who underwent allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2019 in Japan, where medical care was provided within a uniform healthcare system. Center experience was defined based on the number of allogeneic HCTs performed for any indication during the study period, by which centers were divided into low-, intermediate-, and high-volume centers. After adjusting for known confounding factors, the risk of overall mortality was lowest for the high-volume centers and highest for the low-volume centers, with the difference between the center categories attributed primarily to the risk of relapse. Patients transplanted at high-volume centers had higher risks of acute and chronic graft-versus-host diseases but without an increased risk of non-relapse mortality (NRM). These findings reveal the presence of a center effect in allogeneic HCT conducted during the past decade in Japan, highlighting the difference in relapse based on center experience. The weaker effect on NRM compared with that on relapse suggests that the transplantation care quality is becoming equalized across the country.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/complicações , Prognóstico , Recidiva , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/etiologia , Condicionamento Pré-Transplante/efeitos adversos
17.
Exp Hematol ; 132: 104179, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342295

RESUMO

Myeloid leukemia associated with Down syndrome (ML-DS) responds well to chemotherapy and has a favorable prognosis, but the clinical outcome of patients with refractory or relapsed ML-DS is dismal. We recently reported a case of relapsed ML-DS with an effective response to a DNA methyltransferase inhibitor, azacitidine (AZA). However, the efficacy of AZA for refractory or relapsed ML-DS remains uncertain. Here, we investigated the effects and mechanism of action of AZA on three ML-DS cell lines derived from relapsed cases. AZA inhibited the proliferation of all examined ML-DS cell lines to the same extent as that of AZA-sensitive acute myeloid leukemia non-Down syndrome cell lines. Transient low-dose AZA treatment exerted durable antileukemic effects on ML-DS cells. The inhibitory effect included cell cycle arrest, apoptosis, and reduction of aldehyde dehydrogenase activity. Comprehensive differential gene expression analysis showed that AZA induced megakaryocytic differentiation in all ML-DS cell lines examined. Furthermore, AZA induced activation of type I interferon-stimulated genes, primarily involved in antiproliferation signaling, without stimulation of the interferon receptor-mediated autocrine system. Activation of the type I interferon pathway by stimulation with interferon-α exerted antiproliferative effects on ML-DS cells, suggesting that AZA exerts its antileukemic effects on ML-DS cells at least partially through the type I interferon pathway. Moreover, the effect of AZA on normal hematopoiesis did not differ significantly between individuals with non-Down syndrome and Down syndrome. In summary, this study suggests that AZA is a potentially effective treatment option for ML-DS disease control, including relapsed cases, and has reduced side effects.


Assuntos
Azacitidina , Síndrome de Down , Inibidores Enzimáticos , Interferon Tipo I , Leucemia Mieloide Aguda , Humanos , Azacitidina/farmacologia , Azacitidina/uso terapêutico , Linhagem Celular , DNA , Síndrome de Down/complicações , Síndrome de Down/tratamento farmacológico , Síndrome de Down/genética , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Metiltransferases
18.
Thromb Res ; 236: 30-36, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387301

RESUMO

Coagulation disorders frequently complicate the clinical course of acute myeloid leukemia (AML) patients. This study examined the frequency and prognostic significance, with regards of early mortality, of the presence of overt disseminated intravascular coagulation (DIC) at AML diagnosis and its correlation with clinical and biological characteristics. A retrospective analysis of 351 newly diagnosed non-promyelocytic AML patients was conducted, utilizing the 2018 ISTH DIC-Score criteria to evaluate the presence of overt DIC at AML onset. The study cohort had a median age of 65 years with a predominance of male gender (59 %). Overt DIC was present in 21 % of cases and was associated with advanced age, comorbidities, poor performance status, hyperleukocytosis, LDH levels, NPM1 mutations, expression of CD33 and CD4, and lack of expression of CD34. With a median follow-up of 72 months (3-147 months), the 6-year overall survival (OS) was 17.4 %, with patients having overt DIC showing significantly poorer outcomes (7.2 % compared to 20.3 % of those without DIC, p < 0.001). Patients with overt DIC showed markedly high early mortality rates at 30 (42.5 % vs 8 %), 60 (49.3 % vs 16.9 %), and 120 days (64.4 % vs 25.6 %) from disease onset. In multivariate analysis overt DIC retained its independent prognostic value for early mortality. In conclusion, the prevalence and clinical relevance of DIC in non-promyelocytic AML is not negligible, underlining its potential as an unfavorable prognostic marker. In newly diagnosed patients with AML, early recognition and measure to counteract coagulation disturbances might help mitigate the elevated mortality risk associated with DIC.


Assuntos
Coagulação Intravascular Disseminada , Leucemia Mieloide Aguda , Humanos , Masculino , Idoso , Feminino , Coagulação Intravascular Disseminada/etiologia , Estudos Retrospectivos , Leucemia Mieloide Aguda/complicações , Prognóstico , Coagulação Sanguínea
19.
Blood ; 143(11): 971-982, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38232056

RESUMO

ABSTRACT: Acute respiratory failure (ARF) is common in patients with hematological malignancies notably those with acute leukemia, myelodysplastic syndrome, or allogeneic stem cell transplantation. ARF is the leading reason for intensive care unit (ICU) admission, with a 35% case fatality rate. Failure to identify the ARF cause is associated with mortality. A prompt, well-designed diagnostic workup is crucial. The investigations are chosen according to pretest diagnostic probabilities, estimated by the DIRECT approach: D stands for delay, or time since diagnosis; I for pattern of immune deficiency; R and T for radiological evaluation; E refers to clinical experience, and C to the clinical picture. Thorough familiarity with rapid diagnostic tests helps to decrease the use of bronchoscopy with bronchoalveolar lavage, which can cause respiratory status deterioration in those patients with hypoxemia. A prompt etiological diagnosis shortens the time on unnecessary empirical treatments, decreasing iatrogenic harm and costs. High-quality collaboration between intensivists and hematologists and all crossdisciplinary health care workers is paramount. All oxygen delivery systems should be considered to minimize invasive mechanical ventilation. Treatment of the malignancy is started or continued in the ICU under the guidance of the hematologists. The goal is to use the ICU as a bridge to recovery, with the patient returning to the hematology ward in sufficiently good clinical condition to receive optimal anticancer treatment.


Assuntos
Neoplasias Hematológicas , Leucemia Mieloide Aguda , Insuficiência Respiratória , Humanos , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Unidades de Terapia Intensiva , Leucemia Mieloide Aguda/complicações , Doença Aguda , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Insuficiência Respiratória/diagnóstico
20.
JCO Oncol Pract ; 20(4): 503-508, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38261984

RESUMO

PURPOSE: Prophylactic anti-infective strategies are used in patients with cancer to decrease the risk for infection. Dietary restrictions do not allow raw vegetables and fresh fruits to limit the introduction of potentially harmful pathogens in the gastrointestinal tract, but the efficacy is unclear. PATIENTS AND METHODS: In this study analyzing the impact of the dietary restrictions on infectious complications, all children treated between April 2014 and March 2018 for ALL and AML or non-Hodgkin lymphoma (NHL) were included. Dietary restrictions were standard until March 2016, but were stopped in April 2016. Patients with dietary restrictions (treated April 2014-March 2016) and patients not advised for dietary restrictions (treated April 2016-March 2018) were compared regarding infectious complications, including bloodstream infection, pneumonia, diarrhea, and fever of unknown origin (FUO). RESULTS: Eighty-six patients (25 female; 62 ALL; nine AML, 15 NHL) experienced 223 infections. The 46 patients with dietary restrictions and the 40 patients without food restrictions did not significantly differ regarding the number of infections per patient, bloodstream infections, pneumonia, diarrhea, FUO, admission to intensive care, and death. CONCLUSION: Our data suggest that dietary restrictions do not affect the risk for infectious complications. Therefore, the indication of dietary restrictions should be reconsidered in pediatric patients with cancer.


Assuntos
Febre de Causa Desconhecida , Leucemia Mieloide Aguda , Pneumonia , Sepse , Humanos , Criança , Feminino , Febre de Causa Desconhecida/etiologia , Febre de Causa Desconhecida/prevenção & controle , Pneumonia/epidemiologia , Pneumonia/prevenção & controle , Pneumonia/complicações , Leucemia Mieloide Aguda/complicações , Diarreia/epidemiologia , Diarreia/complicações
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